What are the neurological complications of amiodarone?

Neurological Complications of Amiodarone

Amiodarone causes a reversible neurological syndrome characterized by tremor, ataxia, and peripheral neuropathy in approximately 54% of patients, making it the most common reason for altering or discontinuing therapy. 1

Primary Neurological Manifestations

The most frequent neurological complications include:

• Tremor and ataxia occur as the hallmark features of amiodarone neurotoxicity, typically without accompanying nystagmus, dizziness, encephalopathy, or long-tract signs 1
• Peripheral neuropathy develops commonly and can be severe enough to cause disability 1, 2
• Myopathy has been reported and may not always be reversible even after drug withdrawal 2
• Central nervous system effects including dyskinesia, myoclonic jerks, extrapyramidal hypertonia, and altered mental status can occur 3

Optic Complications (Critical Warning)

The FDA warns that optic neuropathy and/or optic neuritis can result in visual impairment progressing to permanent blindness. 4

• Prompt ophthalmologic examination is mandatory if any symptoms of visual impairment appear, including changes in visual acuity or decreases in peripheral vision 4
• Regular ophthalmic examination including fundoscopy and slit-lamp examination is recommended during amiodarone administration 4
• Optic neuropathy/neuritis may occur at any time following initiation of therapy 4

Reversibility and Time Course

• Neurological side effects typically improve or resolve within 2 days to 4 weeks of decreasing or discontinuing amiodarone 1
• However, some neurological complications may be disabling and not always reversible with drug withdrawal, particularly myopathy 2
• Resolution can take up to 3 months in some cases 3

Risk Factors for Neurotoxicity

The following factors increase risk of amiodarone-induced neurological complications:

• Advanced age 3
• Renal failure 3
• Diabetes mellitus 3
• Alcoholism 3

Dose Relationship

• Neurological complications can arise even with usual maintenance doses (200-600 mg daily) 2, 3
• The American Family Physician guidelines emphasize keeping amiodarone dosage at the lowest effective level to minimize toxicity 5
• Most adverse effects are related to total amiodarone exposure (dosage and duration) 5

Clinical Management Algorithm

When neurological symptoms develop:

1. Immediately evaluate for the specific syndrome: tremor, ataxia, peripheral neuropathy, or visual changes 1
2. If visual symptoms occur: arrange urgent ophthalmologic examination with fundoscopy and slit-lamp examination 4
3. Consider dose reduction first if arrhythmia control allows, as symptoms are often dose-related 6
4. Discontinue amiodarone if symptoms are severe or disabling, weighing against the risk of life-threatening arrhythmia recurrence 1, 2
5. Monitor for improvement over 2 days to 4 weeks (up to 3 months in some cases) 1, 3

Critical Pitfall to Avoid

Do not dismiss new neurological symptoms as unrelated to amiodarone simply because the patient is on a "standard" maintenance dose—neurotoxicity occurs frequently and can develop at any dose level, even 200-400 mg daily. 2, 3 The high frequency (54%) of this complication means it should be the first consideration when patients on amiodarone develop tremor, ataxia, or neuropathic symptoms. 1